Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal; Center for Neuroscience and Cell Biology and Institute for Biomedical Imaging and Life Sciences (CNC.IBILI), University of Coimbra, Coimbra, Portugal; Portuguese Institute for Oncology at Coimbra, Coimbra, Portugal.
Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal; Center for Neuroscience and Cell Biology and Institute for Biomedical Imaging and Life Sciences (CNC.IBILI), University of Coimbra, Coimbra, Portugal.
Adv Protein Chem Struct Biol. 2019;115:203-246. doi: 10.1016/bs.apcsb.2018.10.007. Epub 2018 Dec 5.
Cancer is still one of the major causes of death worldwide. Radiation therapy and chemotherapy remain the main treatment modalities in cancer. These therapies exert their effect mainly through interference with DNA replication and induction of DNA damage. It is believed that one way of improving the efficacy of cancer treatment will be to inhibit the replication stress and DNA damage responses and promote mitotic catastrophe of cancer cells. So far, the majority of the efforts have focused central players of checkpoint responses, such as ATR and CHK1, and DNA damage repair, such as PARPs. Being a key player in the replication stress response, checkpoint activation, and the DNA damage response, Claspin constitutes an attractive therapeutic target in cancer, namely for radio- and chemo-sensitization. In this review, we will go through Claspin functions in the replication stress and DNA damage responses and will discuss how Claspin can be targeted in cancer treatment, as well as the effects of Claspin inhibition.
癌症仍然是全球主要死因之一。放射治疗和化学疗法仍然是癌症的主要治疗方式。这些疗法主要通过干扰 DNA 复制和诱导 DNA 损伤来发挥作用。人们认为,提高癌症治疗效果的一种方法将是抑制复制应激和 DNA 损伤反应,促进癌细胞的有丝分裂灾难。到目前为止,大多数努力都集中在检查点反应的核心参与者,如 ATR 和 CHK1,以及 DNA 损伤修复,如 PARPs。作为复制应激反应、检查点激活和 DNA 损伤反应的关键参与者,Claspin 构成了癌症治疗的一个有吸引力的治疗靶点,即放射增敏和化疗增敏。在这篇综述中,我们将回顾 Claspin 在复制应激和 DNA 损伤反应中的功能,并讨论如何在癌症治疗中靶向 Claspin,以及 Claspin 抑制的效果。